Hippocampal Neocortical Coupling Varies as a Function of Depth of NREM Sleep

During NREM sleep, the brain is in a self-organized excitable regime in which alternations between spiking and near cessation of spiking propagate along the forebrain, termed slow oscillations (SOs) or UP and DOWN states in the neocortex, and sharpwave-ripples (SPW-Rs) in the hippocampus (Levenstein 2019). Both gain and loss of function studies have demonstrated the importance of tight temporal coordination between SOs and SPW-Rs for systems consolidation. However, where and how this coordination is spontaneously achieved is unknown, despite being essential for understanding whole-brain mechanisms of systems consolidation. Towards this, we develop a preparation in mice that combines widefield imaging of dorsal neocortex and extracellular silicon probe recordings of hippocampus (HPC) and retrosplenial cortex (RSC), allowing us to monitor multi-scale interaction between regions during sleep, and further develop an existing mean-field model of NREM. We find that interaction between HPC and RSC is well matched by a proposed model whereby both RSC and HPC are in reciprocally perturbable excitable regimes, and the degree to which they can perturb one another depends on both the strength of input received and state of the receiving region. This occurs in three phases, or a neocortical-hippocampal-neocortical loop. First, hippocampal SPW-Rs are preceded by increased fluorescence in mouse visual and association cortices. The number of regions active preceding the SPW-R predicts the magnitude of sharpwave associated with the ripple, thought to reflect the degree of input to the region. The greater the magnitude of input, the larger the amplitude of the evoked ripple, and the larger the DOWN state evoked in CTX. This evoked DOWN is most likely to occur in retrosplenial cortex, and the extent to which it propagates down the cortical hierarchy varies as a function of the depth of NREM.